AR035957A1 - PROCEDURE FOR THE PREPARATION OF 1,3-SUBSTITUTES AND AZAPOLICICLIC COMPOUNDS CONDENSED WITH ARILOS - Google Patents

PROCEDURE FOR THE PREPARATION OF 1,3-SUBSTITUTES AND AZAPOLICICLIC COMPOUNDS CONDENSED WITH ARILOS

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AR035957A1
AR035957A1 ARP020101424A ARP020101424A AR035957A1 AR 035957 A1 AR035957 A1 AR 035957A1 AR P020101424 A ARP020101424 A AR P020101424A AR P020101424 A ARP020101424 A AR P020101424A AR 035957 A1 AR035957 A1 AR 035957A1
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alkyl
alkoxy
fluorine
carbon atoms
aryl
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Pfizer Prod Inc
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Abstract

Procedimiento para la preparación de cualquiera de los indenos 1,3-sustituidos intermedios de las fórmulas (1), (2) y (3) o una mezcla de los mismos, en donde R2 y R3 se seleccionan, independientemente, entre hidrógeno, flúor, cloro, -SOq-alquilo C1-6, siendo q cero, uno o dos, (alquil C1-6)2-amino, -CO2R7, -CONR8R9, -SO2NR10R11, aril-alquil(C0-3)- ó aril-alquil(C0-3)-O-, seleccionándose dicho arilo entre fenilo y naftilo, heteroaril-alquil(C0-3)- ó heteroaril-alquil(C0-3)-O-, seleccionándose dicho heteroarilo entre anillos aromáticos de cinco a siete miembros que contienen de uno a cuatro heteroátomos seleccionados entre oxígeno, nitrógeno y azufre; X2-alquil(C0-6)- y X2-alcoxi(C1-6)-alquil(C0-6)-, estando X2 ausente o siendo X2 alquil(C1-6)-amino- ó (alquil(C1-6))2-amino y conteniendo los restos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- de dichos X2-alquil(C0-6)- ó X2-alcoxi(C1-6)-alquil(C0-6)- al menos un átomo de carbono y pudiendo reemplazarse opcionalmente de uno a tres de los átomos de carbono de dichos restos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- por un átomo de oxígeno, nitrógeno o azufre, con la condición de que dos cualesquiera de dichos heteroátomos deben estar separados por al menos dos átomos de carbono y pudiendo estar cualquiera de los restos alquilo de dichos grupos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- opcionalmente sustituido con dos a siete átomos de flúor y pudiendo reemplazarse opcionalmente uno de los átomos de carbono de cada uno de los restos alquilo de dicho aril-alquil(C0-3)- y dicho heteroaril-alquil(C0-3)- por un átomo de oxígeno, nitrógeno o azufre, y pudiendo estar opcionalmente sustituido cada uno de los grupos arilo y heteroarilo anteriores con uno o más sustituyentes, preferiblemente de cero a dos sustituyentes, seleccionados independientemente entre alquilo C1-6 opcionalmente sustituido con uno a siete átomos de flúor, alcoxi C1-6 opcionalmente sustituido con dos a siete átomos de flúor, cloro, flúor, (alquil(C1-6))2-amino-, -CO2R7, -CONR8R9 y -SO2NR10R11; ó R2 y R3, junto con los carbonos a los que están unidos, forman un anillo carbocíclico monocíclico de cuatro a siete miembros, o bicíclico de diez a catorce miembros, que puede estar saturado o insaturado, pudiendo reemplazarse opcional e independientemente de uno a tres de los átomos de carbono no condensados de dichos anillos monocíclicos y de uno a cinco de los átomos de carbono de dichos anillos bicíclicos que no forman parte del anillo de benceno mostrado en la fórmula (4), por un nitrógeno, oxígeno o azufre y pudiendo estar opcionalmente sustituidos dichos anillos monocíclicos y bicíclicos con uno o más sustituyentes, preferiblemente de cero a dos sustituyentes para los anillos monocíclicos y de cero a tres sustituyentes para los anillos bicíclicos, que se seleccionan, independientemente, entre alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)-, sin que el número total de átomos de carbono exceda de seis y pudiendo estar opcionalmente sustituido cualquiera de los restos alquilo con uno a siete átomos de flúor; oxo, flúor, cloro, (alquil C1-6)2-amino-, -CO2R7, -CONR8R9 y -SO2NR10R11; cada uno de R7, R8, R9, R10 y R11 se selecciona, independientemente, entre hidrógeno y alquilo C1-6, ó R8 y R9, ó R10 y R11, junto con el nitrógeno al que están unidos, forman un anillo de pirrolidina, piperidina, morfolina, azetidina, piperazina, -N-alquil(C1-6)-piperazina o tiomorfolina, o un anillo de tiomorfolina en el que el azufre del anillo se reemplaza por un sulfóxido o sulfona; y cada X es, independientemente, alquileno C1-6; R5 es alquilo C1-6 o Si(R12)3; R1 es un grupo de extracción de electrones seleccionado entre ciano, alcoxicarbonilo, alquilcarbonilo, arilcarbonilo, arilo, nitro, trifluorometilo y sulfonilo; cada R4 es independientemente H, alquilo C1-6, H(L)3N+, o un catión metálico, incluyendo cationes de metales alcalinos de Na, K, Li o Cs; o dos grupos R11 conjuntamente forman un enlace alquileno C2-3; cada L es independientemente H, alquilo C1-6, fenilo o bencilo; y cada R12 es independientemente alquilo C1-6 o fenilo. Los compuestos de fórmulas (1), (2) y (3), o las mezclas de los mismos, son útiles en la preparación de compuestos de fórmula (4) en la que R6 es hidrógeno; en la que R2 y R3 se seleccionan, independientemente, entre hidrógeno, flúor, cloro, -SOq-alquilo C1-6, siendo q cero, uno o dos, (alquil C1-6)2-amino, -CO2R7, -CONR8R9, -SO2NR10R11, aril-alquil(C0-3)- ó aril-alquil(C0-3)-O-, seleccionándose dicho arilo entre fenilo y naftilo, heteroaril-alquil(C0-3)- ó heteroaril-alquil(C0-3)-O-, seleccionándose dicho heteroarilo entre anillos aromáticos de cinco a siete miembros que contienen de uno a cuatro heteroátomos seleccionados entre oxígeno, nitrógeno y azufre; X2-alquil(C0-6)- y X2-alcoxi(C1-6)-alquil(C0-6)-, estando X2 ausente o siendo X2 alquil(C1-6)-amino- ó (alquil(C1-6))2-amino y conteniendo los restos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- de dichos X2-alquil(C0-6)- ó X2-alcoxi(C1-6)-alquil(C0-6)- al menos un átomo de carbono y pudiendo reemplazarse opcionalmente de uno a tres de los átomos de carbono de dichos restos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- por un átomo de oxígeno, nitrógeno o azufre, con la condición de que dos cualesquiera de dichos heteroátomos deben estar separados por al menos dos átomos de carbono y pudiendo estar cualquiera de los restos alquilo de dichos grupos alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)- opcionalmente sustituido con dos a siete átomos de flúor y pudiendo reemplazarse opcionalmente uno de los átomos de carbono de cada uno de los restos alquilo de dicho aril-alquil(C0-3)- y dicho heteroaril-alquil(C0-3)- por un átomo de oxígeno, nitrógeno o azufre, y pudiendo estar opcionalmente sustituido cada uno de los grupos arilo y heteroarilo anteriores con uno o más sustituyentes, preferiblemente de cero a dos sustituyentes, seleccionados independientemente entre alquilo C1-6 opcionalmente sustituido con uno a siete átomos de flúor, alcoxi C1-6 opcionalmente sustituido con dos a siete átomos de flúor, cloro, flúor, (alquil(C1-6))2-amino-, -CO2R7, -CONR8R9 y -SO2NR10R11; ó R2 y R3, junto con los carbonos a los que están unidos, forman un anillo carbocíclico monocíclico de cuatro a siete miembros, o bicíclico de diez a catorce miembros, que puede estar saturado o insaturado, pudiendo reemplazarse opcional e independientemente de uno a tres de los átomos de carbono no condensados de dichos anillos monocíclicos y de uno a cinco de los átomos de carbono de dichos anillos bicíclicos que no forman parte del anillo de benceno mostrado en la fórmula (4), por un nitrógeno, oxígeno o azufre y pudiendo estar opcionalmente sustituidos dichos anillos monocíclicos y bicíclicos con uno o más sustituyentes, preferiblemente de cero a dos sustituyentes para los anillos monocíclicos y de cero a tres sustituyentes para los anillos bicíclicos, que se seleccionan, independientemente, entre alquil(C0-6)- ó alcoxi(C1-6)-alquil(C0-6)-, sin que el número total de átomos de carbono exceda de seis y pudiendo estar opcionalmente sustituido cualquiera de los restos alquilo con uno a siete átomos de flúor; oxo, flúor, cloro, (alquil C1-6)2-amino-, -CO2R7, -CONR8R9 y -SO2NR10R11; cada uno de R7, R8, R9, R10 y R11 se selecciona, independientemente, entre hidrógeno y alquilo C1-6, ó R8 y R9, ó R10 y R11, junto con el nitrógeno al que están unidos, forman un anillo de pirrolidina, piperidina, morfolina, azetidina, piperazina, -N-alquil(C1-6)-piperazina o tiomorfolina, o un anillo de tiomorfolina en el que el azufre del anillo se reemplaza por un sulfóxido o sulfona; y cada X es, independientemente, alquileno C1-6.Process for the preparation of any of the intermediate 1,3-substituted indes of formulas (1), (2) and (3) or a mixture thereof, wherein R2 and R3 are independently selected from hydrogen, fluorine , chlorine, -SOq-C1-6 alkyl, where q is zero, one or two, (C1-6 alkyl) 2-amino, -CO2R7, -CONR8R9, -SO2NR10R11, aryl-alkyl (C0-3) - or aryl- (C0-3) alkyl -O-, said aryl being selected from phenyl and naphthyl, heteroaryl (C0-3) alkyl- or heteroaryl-C0-3-alkyl-O-, said heteroaryl being selected from aromatic rings of five to seven members containing one to four heteroatoms selected from oxygen, nitrogen and sulfur; X2-alkyl (C0-6) - and X2-alkoxy (C1-6) -alkyl (C0-6) -, being X2 absent or being X2 alkyl (C1-6) -amino- or (alkyl (C1-6) ) 2-amino and containing the alkyl (C0-6) - or (C1-6) alkoxy (C0-6) - of said X2-alkyl (C0-6) - or X2-alkoxy (C1-6) moieties -alkyl (C0-6) - at least one carbon atom and can optionally be replaced from one to three of the carbon atoms of said alkyl (C0-6) moieties - or (C1-6) alkoxy -alkyl (C0-6 ) - by an oxygen, nitrogen or sulfur atom, with the proviso that any two of said heteroatoms must be separated by at least two carbon atoms and any of the alkyl moieties of said alkyl groups (C0-6) can be - or (C1-6) alkoxy (C0-6) alkyl - optionally substituted with two to seven fluorine atoms and one of the carbon atoms of each of the alkyl moieties of said aryl-alkyl (C0-3) may optionally be replaced ) - and said heteroaryl (C0-3) alkyl - by an oxygen, nitrogen or sulfur atom, and may be option Ally substituted each of the above aryl and heteroaryl groups with one or more substituents, preferably from zero to two substituents, independently selected from C1-6 alkyl optionally substituted with one to seven fluorine atoms, C1-6 alkoxy optionally substituted with two to seven atoms of fluorine, chlorine, fluorine, ((C1-6) alkyl) 2-amino-, -CO2R7, -CONR8R9 and -SO2NR10R11; or R2 and R3, together with the carbons to which they are attached, form a monocyclic carbocyclic ring of four to seven members, or bicyclic of ten to fourteen members, which may be saturated or unsaturated, and may be optionally and independently replaced from one to three of the non-condensed carbon atoms of said monocyclic rings and one to five of the carbon atoms of said bicyclic rings that are not part of the benzene ring shown in the formula (4), by a nitrogen, oxygen or sulfur and being able said monocyclic and bicyclic rings are optionally substituted with one or more substituents, preferably from zero to two substituents for the monocyclic rings and from zero to three substituents for the bicyclic rings, which are independently selected from (C0-6) alkyl- or (C1-6) alkoxy-(C0-6) -alkyl, without the total number of carbon atoms exceeding six and any of the res may be optionally substituted Cough alkyl with one to seven fluorine atoms; oxo, fluorine, chlorine, (C1-6 alkyl) 2-amino-, -CO2R7, -CONR8R9 and -SO2NR10R11; each of R7, R8, R9, R10 and R11 is independently selected from hydrogen and C1-6 alkyl, or R8 and R9, or R10 and R11, together with the nitrogen to which they are attached, form a pyrrolidine ring, piperidine, morpholine, azetidine, piperazine, -N-(C1-6) alkylpiperazine or thiomorpholine, or a thiomorpholine ring in which the ring sulfur is replaced by a sulfoxide or sulfone; and each X is, independently, C1-6 alkylene; R5 is C1-6 alkyl or Si (R12) 3; R1 is an electron extraction group selected from cyano, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aryl, nitro, trifluoromethyl and sulfonyl; each R4 is independently H, C1-6 alkyl, H (L) 3N +, or a metal cation, including alkali metal cations of Na, K, Li or Cs; or two R11 groups together form a C2-3 alkylene bond; each L is independently H, C1-6 alkyl, phenyl or benzyl; and each R12 is independently C1-6 alkyl or phenyl. The compounds of formulas (1), (2) and (3), or mixtures thereof, are useful in the preparation of compounds of formula (4) in which R 6 is hydrogen; wherein R2 and R3 are independently selected from hydrogen, fluorine, chlorine, -SOq-C1-6 alkyl, where zero, one or two, (C1-6 alkyl) 2-amino, -CO2R7, -CONR8R9, -SO2NR10R11, aryl-alkyl (C0-3) - or aryl-alkyl (C0-3) -O-, said aryl being selected from phenyl and naphthyl, heteroaryl-alkyl (C0-3) - or heteroaryl-alkyl (C0-3) ) -O-, said heteroaryl being selected from five to seven member aromatic rings containing one to four heteroatoms selected from oxygen, nitrogen and sulfur; X2-alkyl (C0-6) - and X2-alkoxy (C1-6) -alkyl (C0-6) -, being X2 absent or being X2 alkyl (C1-6) -amino- or (alkyl (C1-6) ) 2-amino and containing the alkyl (C0-6) - or (C1-6) alkoxy (C0-6) - of said X2-alkyl (C0-6) - or X2-alkoxy (C1-6) moieties -alkyl (C0-6) - at least one carbon atom and can optionally be replaced from one to three of the carbon atoms of said alkyl (C0-6) moieties - or (C1-6) alkoxy -alkyl (C0-6 ) - by an oxygen, nitrogen or sulfur atom, with the proviso that any two of said heteroatoms must be separated by at least two carbon atoms and any of the alkyl moieties of said alkyl groups (C0-6) can be - or (C1-6) alkoxy (C0-6) alkyl - optionally substituted with two to seven fluorine atoms and one of the carbon atoms of each of the alkyl moieties of said aryl-alkyl (C0-3) may optionally be replaced ) - and said heteroaryl (C0-3) alkyl - by an oxygen, nitrogen or sulfur atom, and may be option Ally substituted each of the above aryl and heteroaryl groups with one or more substituents, preferably from zero to two substituents, independently selected from C1-6 alkyl optionally substituted with one to seven fluorine atoms, C1-6 alkoxy optionally substituted with two to seven atoms of fluorine, chlorine, fluorine, ((C1-6) alkyl) 2-amino-, -CO2R7, -CONR8R9 and -SO2NR10R11; or R2 and R3, together with the carbons to which they are attached, form a monocyclic carbocyclic ring of four to seven members, or bicyclic of ten to fourteen members, which may be saturated or unsaturated, and may be optionally and independently replaced from one to three of the non-condensed carbon atoms of said monocyclic rings and one to five of the carbon atoms of said bicyclic rings that are not part of the benzene ring shown in the formula (4), by a nitrogen, oxygen or sulfur and being able said monocyclic and bicyclic rings are optionally substituted with one or more substituents, preferably from zero to two substituents for the monocyclic rings and from zero to three substituents for the bicyclic rings, which are independently selected from (C0-6) alkyl- or (C1-6) alkoxy-(C0-6) -alkyl, without the total number of carbon atoms exceeding six and any of the res may be optionally substituted Cough alkyl with one to seven fluorine atoms; oxo, fluorine, chlorine, (C1-6 alkyl) 2-amino-, -CO2R7, -CONR8R9 and -SO2NR10R11; each of R7, R8, R9, R10 and R11 is independently selected from hydrogen and C1-6 alkyl, or R8 and R9, or R10 and R11, together with the nitrogen to which they are attached, form a pyrrolidine ring, piperidine, morpholine, azetidine, piperazine, -N-(C1-6) alkylpiperazine or thiomorpholine, or a thiomorpholine ring in which the ring sulfur is replaced by a sulfoxide or sulfone; and each X is independently C1-6 alkylene.

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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60234268D1 (en) * 2001-11-16 2009-12-17 Cdt Oxford Ltd LUMINAIRE DIODE AND USED CONNECTIONS
RS20050393A (en) * 2002-11-25 2007-12-31 Pfizer Products Inc., Improved process for the preparation of 1,3-substituted indenes
WO2004063164A1 (en) * 2003-01-15 2004-07-29 Pfizer Products Inc. Process for the preparation of aryl fused polycyclic lactams
DE602004015986D1 (en) * 2003-06-04 2008-10-02 Pfizer Prod Inc PREPARATION OF SUBSTITUTED CHINOXALINES FROM DIANILINES WITH 2,3-DIHYDROXY-1,4-DIOXANE
CA2533100A1 (en) * 2003-07-21 2005-01-27 Pfizer Products Inc. Aryl fused azapolycyclic compounds
EP1951668B1 (en) * 2005-11-16 2010-04-14 F.Hoffmann-La Roche Ag Novel process for the preparation of thoc
DE102006024903A1 (en) * 2006-05-24 2007-11-29 Basf Ag A method for preventing fumaric acid deposits in the production of maleic anhydride
RS52074B (en) 2007-05-16 2012-06-30 Nycomed Gmbh Pyrazolone derivatives as pde4 inhibitors
EP2019107A1 (en) 2007-07-26 2009-01-28 Dynamit Nobel GmbH Explosivstoff- und Systemtechnik Use of phosphonium salts in coupling reactions and process for their manufacture
WO2009065872A2 (en) * 2007-11-20 2009-05-28 Medichem, S.A. Improved processes for the synthesis of varenicline l-tartrate
EP2260037A2 (en) * 2008-02-15 2010-12-15 Medichem, S.A. A polymorphic form of a pyrazino [2,3-h] [3] benzazepine derivative
CA2709774C (en) 2008-05-22 2012-10-02 Teva Pharmaceutical Industries Ltd. Varenicline tosylate, an intermediate in the preparation process of varenicline l-tartrate
WO2009155403A2 (en) * 2008-06-19 2009-12-23 Teva Pharmaceutical Industries Ltd. Processes for the preparation of varenicline and intermediates thereof
WO2010005643A1 (en) * 2008-07-10 2010-01-14 Teva Pharmaceutical Industries Ltd. Processes for purifying varenicline l-tartrate salt and preparing crystalline forms of varenicline l-tartrate salt
WO2010151524A1 (en) 2009-06-22 2010-12-29 Teva Pharmaceutical Industries Ltd Solid states forms of varenicline salts and processes for preparation thereof
US20120004239A1 (en) 2010-06-11 2012-01-05 Medichem, S.A. Process for Preparing Quinoxaline Derivatives
KR101603427B1 (en) * 2014-08-14 2016-03-15 영남대학교 산학협력단 Efficient synthesis of indene derivatives by cascade reactions
CN104478803A (en) * 2014-12-19 2015-04-01 连云港恒运医药科技有限公司 Preparation method of varenicline intermediate and nitroreduction impurity thereof
KR20180041154A (en) * 2015-08-14 2018-04-23 보울로스 ＆ 쿠퍼 파마슈티컬스 피티와이 리미티드 Synthesis of aryl compounds
CN110023331B (en) 2016-07-07 2024-09-17 霍华休斯医学研究院 Modified ligand-gated ion channels and methods of use
US10961296B2 (en) * 2017-11-10 2021-03-30 Howard Hughes Medical Institute Modified ligand-gated ion channels and methods of use
CN111995519B (en) * 2020-09-26 2022-08-26 安徽金禾实业股份有限公司 Preparation method of 3-methoxy methyl acrylate
CN115322105A (en) * 2021-05-11 2022-11-11 江苏润安制药有限公司 Method for synthesizing Iguratimod key intermediate

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5479598A (en) * 1992-10-23 1995-12-26 International Business Machines Corporation Compact graphical parallel program user output interface controlled directly by the parallel computer program
DE69409445D1 (en) * 1993-07-27 1998-05-14 Ibm Process monitoring in a multiple processing provider
US6289368B1 (en) * 1995-12-27 2001-09-11 First Data Corporation Method and apparatus for indicating the status of one or more computer processes
US5928323A (en) * 1996-05-30 1999-07-27 Sun Microsystems, Inc. Apparatus and method for dynamically generating information with server-side software objects
FR2751448B1 (en) * 1996-07-17 1999-01-15 Bull Sa METHOD FOR REAL-TIME MONITORING OF A COMPUTER SYSTEM FOR ITS ADMINISTRATION AND ASSISTANCE IN MAINTAINING IT IN OPERATION
US6112194A (en) * 1997-07-21 2000-08-29 International Business Machines Corporation Method, apparatus and computer program product for data mining having user feedback mechanism for monitoring performance of mining tasks
US6119165A (en) * 1997-11-17 2000-09-12 Trend Micro, Inc. Controlled distribution of application programs in a computer network
US6100887A (en) * 1997-12-05 2000-08-08 At&T Corporation Reusable reversible progress indicator software component for a graphical user interface
US6605610B1 (en) * 1997-12-31 2003-08-12 Pfizer Inc Aryl fused azapolycyclic compounds
HU230297B1 (en) * 1997-12-31 2015-12-28 Pfizer Products Inc. Aryl fused azapolycyclic compounds
US6151357A (en) * 1998-01-16 2000-11-21 Aspect Communications Corporation Method and apparatus for displaying a visual indication of a transmission status
US6108003A (en) * 1998-03-18 2000-08-22 International Business Machines Corporation Maintaining visibility and status indication of docked applications and application bars
NZ507035A (en) * 1998-04-29 2003-05-30 Pfizer Prod Inc Aryl fused azapolycyclic compounds
FR2788982B1 (en) * 1999-02-02 2002-08-02 Synthelabo PHARMACEUTICAL COMPOSITIONS CONTAINING NICOTINE AND THEIR APPLICATION IN SMOKING WITHDRAWAL
AU5667100A (en) * 1999-07-02 2001-01-22 Prescient Neuropharma Inc. Novel aminoindanes
IL137937A0 (en) * 1999-08-27 2001-10-31 Pfizer Prod Inc A pharmaceutical composition for the prevention and treatment of nicotine addiction in a mammal
US20010036943A1 (en) * 2000-04-07 2001-11-01 Coe Jotham W. Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines
US20010036949A1 (en) * 2000-05-09 2001-11-01 Coe Jotham Wadsworth Pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal
US20020010192A1 (en) * 2000-06-02 2002-01-24 Coe Jotham Wadsworth Pharmaceutical composition for the treatment of obesity or to facilitate or promote weight loss
US20020016334A1 (en) * 2000-07-31 2002-02-07 Coe Jotham Wadsworth Pharmaceutical composition for the treatment of attention deficit hyperactivity disorder (ADHD)

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